Nature communications · 2018
Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Brenner Jacob S, Pan Daniel C, Myerson Jacob W, Marcos-Contreras Oscar A, Villa Carlos H, Patel Priyal, Hekierski Hugh, Chatterjee Shampa, Tao Jian-Qin, Parhiz Hamideh, Bhamidipati Kartik, Uhler Thomas G, Hood Elizabeth D, Kiseleva Raisa Yu, Shuvaev Vladimir S, Shuvaeva Tea, Khoshnejad Makan, Johnston Ian, Gregory Jason V, Lahann Joerg, Wang Tao, Cantu Edward, Armstead William M, Mitragotri Samir, Muzykantov Vladimir
Аннотация
Drug delivery by nanocarriers (NCs) has long been stymied by dominant liver uptake and limited target organ deposition, even when NCs are targeted using affinity moieties. Here we report a universal solution: red blood cell (RBC)-hitchhiking (RH), in which NCs adsorbed onto the RBCs transfer from RBCs to the first organ downstream of the intravascular injection. RH improves delivery for a wide range of NCs and even viral vectors. For example, RH injected intravenously increases liposome uptake in the first downstream organ, lungs, by ~40-fold compared with free NCs. Intra-carotid artery injection of RH NCs delivers >10% of the injected NC dose to the brain, ~10× higher than that achieved with affinity moieties. Further, RH works in mice, pigs, and ex vivo human lungs without causing RBC or end-organ toxicities. Thus, RH is a clinically translatable platform technology poised to augment drug delivery in acute lung disease, stroke, and several other diseases.